Endothelium-Derived Nitric Oxide Contributes to the Regulation of Venous Tone in Humans

Abstract

Background-Although nitric oxide (NO) is known to play an important part in the regulation of arterial tone, little is known about its role in veins. The aim of this study was to investigate the role of basal and stimulated NO activity in the regulation of tone of the human venous capacitance bed. Methods and Results-We measured venous tone using radionuclide forearm venous plethysmography in 24 healthy subjects with no cardiovascular risk factors. In 13 subjects, basal NO activity was assessed by measuring the effects on venous tone of an intra-arterial infusion of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA). In the remaining 11 subjects, stimulated NO activity was evaluated by measuring the effects of an intra-arterial infusion of incremental doses of carbachol, followed in a subgroup by coinfusion with L-NMMA. Infusion of carbachol caused dose-dependent venodilation, with a maximal reduction in forearm venous tone of 40.1Ϯ12.5% (PϽ0.0001). Carbachol-induced venodilation was inhibited by L-NMMA (48.9Ϯ6.2% reversal of maximal venodilation, PϽ0.01).Infusion of L-NMMA alone caused venoconstriction (9.1Ϯ6.4% increase in venous tone, Pϭ0.002). Conclusions-Human forearm capacitance veins exhibit both stimulated and basal NO activity, which indicates that NO contributes not only to the regulation of venous tone but also to resting venous tone in healthy human subjects.

Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

“…Despite evidence for a well-defined role of NO in the venous vasculature (14,40), NOS inhibition in either group did not result in differences in venous vascular function measured by the VVV. Deep veins of the legs have sparse SNS innervation; thus, their compliance is primarily controlled by surrounding skeletal muscles under normal physiologic conditions (41).…”

Testing Endothelial Function and its Clinical Relevance

“…Deteriorated vessel wall function (venous or arterial) could promote thrombus formation. The link between endothelial dysfunction and venous thrombosis has been established in several studies 46) and, interestingly, endothelial microparticles, which have been shown to regulate venous tone, were detected in patients with venous thrombosis 47,48) . Since more than 70% of the total circulating blood volume is contained in the venous vascular bed, it is conceivable that small changes in venous tone may substantially affect filling pressure, making the evaluation of venous endothelial function an attractive new method to evaluate vascular homeostasis.…”

Endothelium, venous thromboembolism and ischaemic cardiovascular events

“…by assessing ex vivo the contraction of rings of vein tissue excised at surgery (30,31), or by a minimally invasive method which assesses the diameter of a dorsal vein of the hand in response to pharmacologic stimuli (32). The studies so far performed using these methods show that NO plays a central role in the regulation of venous endothelial function, similarly to what it does for arterial endothelial function (33,34). Interestingly, what emerges from these studies is that conditions associated with arterial endothelial dysfunction, like hypertension, smoking, diabetes, coronary artery disease, heart failure and renal failure, are also characterised by a dysfunction of venous endothelium (30,31,(35)(36)(37)(38)(39)(40)(41)(42) …”